crossing96/oncoscreening huggingface dataset:
Autophagy is induced by adenoviral-mediated interferon alpha treatment in interferon resistant bladder cancer and normal urothelial cells as a cell death protective mechanism but not by the bystander factors produced.	We have previously shown that adenoviral-mediated interferon alpha (Ad-IFNalpha) treatment is highly cytotoxic to tumor cells which are resistant to the IFNalpha protein. We now report that autophagy is produced after Ad-IFNalpha treatment of either IFN resistant bladder cancer cells (UC9 and KU7) or the normal urothelial cell line (TERT-NHUC). After Ad-IFNalpha infection autophagosomes, an early stage of autophagy, were seen in cancer cells whereas autophagolysosomes, a later stage of autophagy, were observed mostly in normal cells by electron microscopy. Conditioned medium from either normal or bladder cancer cells obtained after Ad-IFNalpha infection, however, produced no autophagy when placed on the bladder cancer cells, although again marked cytotoxicity was observed. This indicated that the autophagy seen was related to the direct effect of Ad-IFNalpha transfection and expression rather than to the bystander factors produced. In addition, autophagic changes were seen using LysoTracker Red DND-99 in both normal and cancer cells. We also documented that Ad-IFNalpha treatment produces the autophagic protein form, light chain 3 (LC3)-II, in cancer cells but not normal cells, which in turn was inhibited by the autophagic inhibitor, 3-methyladenine (3-MA). This inhibition of autophagy resulted in a significant increase in apoptotic cell death as measured by the sub-G1 population. We hypothesize that the autophagy seen in normal urothelial cells is a protective response and is allowed to be completed, providing a survival mechanism after Ad-IFN treatment, whereas the autophagy produced in IFN resistant cancer cells is not allowed to be completed and is insufficient to significantly suppress cytotoxicity.	bladder
Reduction of major histocompatibility complex class I expression on bladder carcinoma following tumor antigen-pulsed dendritic cell vaccine: Implications for immunoresistance in therapy.	OBJECTIVES: To clarify the relationship between a decreased major histocompatibility complex class I (MHC-I) expression on bladder tumors and decreased immunological efficacy of tumor antigen-pulsed dendritic cell vaccine in a rat bladder carcinoma model induced by N-methyl-N-nitrosourea irrigation. METHODS: Enzyme-linked immunosorbent assay was used to evaluate interferon-gamma concentration in the serum and colorimetric lactate dehydrogenase release assay in vitro was used to test the cytotoxicity capability of T lymphocytes. MHC-I expression on tumor cells was detected by flow cytometry and analyzed with CellQuest software. RESULTS: The tumor antigen sensitized dendritic cell vaccine group showed decreased hyperplastic formations, lower pathological stages in rat bladders and more potent cytotoxicity activity (P < 0.001) than the dendritic cell vaccine group. Additionally, immunization with pulsed dendritic cell vaccine induced higher specific cytokine production of interferon-gamma. Nevertheless, a decreased MHC-I expression on bladder tumors was tested after immunotherapy by pulsed dendritic cell vaccine on week 15. As expected, the cytotoxic activity of T lymphocytes from rats on tumor cells with low MHC-I expression was also decreased to 19.70 +/- 4.82% as compared with tumor cells with high MHC-I (52.10 +/- 8.66%, P = 0.005). CONCLUSIONS: Tumor antigen sensitized dendritic cell vaccine has beneficial activity on N-methyl-N-nitrosourea-induced bladder cancer in situ in rats, but therapeutic responses are accompanied by decreased MHC-I expression on tumors, possibly suggesting poor long-term therapeutic outcomes.	bladder
Depletion of regulatory T cells by anti-GITR mAb as a novel mechanism for cancer immunotherapy.	In vitro, engagement of GITR on Treg cells by the agonistic anti-GITR mAb, DTA-1, appears to abrogate their suppressive function. The consequence of in vivo engagement of GITR by DTA-1 is, however, less clear. In this study, we show that Treg cells isolated from DTA-1-treated mice were as potent as those from untreated mice in suppressing conventional CD4 T cells in vitro, indicating that in vivo GITR ligation does not disable Treg cells. Treatment of Foxp3/GFP knock-in mice with DTA-1 led to a selective reduction of circulating Treg cells, suggesting that DTA-1 is a depleting mAb which preferentially targets Treg cells. In tumour-bearing mice, DTA-1-mediated depletion of Treg cells was most marked in tumours but not in tumour-draining lymph node. These features were confirmed in an adoptive transfer model using tumour antigen-specific Treg cells. Interestingly, Treg cells detected in tumour tissues expressed much higher levels of GITR than those in tumour-draining lymph nodes, indicating that the efficiency of depletion might be correlated with the level of GITR expression. Finally, in vivo labelling of GITR in naive or tumour-bearing mice demonstrated that Treg cells constitutively expressed higher levels of GITR than conventional T cells, independent of location and activation state, consistent with the preferential in vivo depletion of Tregs by DTA-1. Thus, depletion of Treg cells represents a previously unrecognised in vivo activity of DTA-1 which has important implications for the application of anti-GITR antibodies in cancer immunotherapy.	bladder
The RNA binding protein Musashi1 regulates apoptosis, gene expression and stress granule formation in urothelial carcinoma cells.	The RNA-binding protein Musashi1 (MSI1) is a marker of progenitor cells in the nervous system functioning as a translational repressor. We detected MSI1 mRNA in several bladder carcinoma cell lines, but not in cultured normal uroepithelial cells, whereas the paralogous MSI2 gene was broadly expressed. Knockdown of MSI1 expression by siRNA induced apoptosis and a severe decline in cell numbers in 5637 bladder carcinoma cells. Microarray analysis of gene expression changes after MSI1 knockdown significantly up-regulated 735 genes, but down-regulated only 31. Up-regulated mRNAs contained a highly significantly greater number and density of Musashi binding sites. Therefore, a much larger set of mRNAs may be regulated by Musashi1, which may affect not only their translation, but also their turnover. The study confirmed p21(CIP1) and Numb proteins as targets of Musashi1, suggesting additionally p27(KIP1) in cell-cycle regulation and Jagged-1 in Notch signalling. A significant number of up-regulated genes encoded components of stress granules (SGs), an organelle involved in translational regulation and mRNA turnover, and impacting on apoptosis. Accordingly, heat shock induced SG formation was augmented by Musashi1 down-regulation. Our data show that ectopic MSI1 expression may contribute to tumorigenesis in selected bladder cancers through multiple mechanisms and reveal a previously unrecognized function of Musashi1 in the regulation of SG formation.	bladder
Comparison of outcomes based on treatment algorithms for rhabdomyosarcoma of the bladder/prostate: combined results from the Children's Oncology Group, German Cooperative Soft Tissue Sarcoma Study, Italian Cooperative Group, and International Society of Pediatric Oncology Malignant Mesenchymal Tumors Committee.	The purpose of this study was to determine patient characteristics and outcomes for bladder/prostate (BP) rhabdomyosarcoma (RMS) using an international cohort of prospectively treated patients comparing different treatment algorithms. Data were collected from 379 patients (1979-1998) treated on protocol; Intergroup Rhabdomyosarcoma Study, IRS-IV (n = 239 patients), International Society of Pediatric Oncology Malignant Mesenchymal Tumors (MMT) Committee MMT-84 and -89 (n = 74), Italian Cooperative Group, RMS-79 and RMS-88 Studies (n = 37) or German Cooperative Soft Tissue Sarcoma Study CWS-91 protocols (n = 29). A total of 322 (85%) patients had localized embryonal RMS (ERMS) and 27 had metastatic disease. Thirty patients (21 local disease; 9 metastatic) had nonembryonal BP RMS. Patients with localized ERMS had large tumors (64% >5 cm) that were invasive (54%) with uninvolved regional lymph nodes (N0, 93%). The 5-year failure-free survival (FFS) was 75% and the overall survival (OS) was 84%, with 89% of deaths attributed to disease. Treatment failures were usually local disease recurrence (60%). Predictors of FFS included T-stage (invasiveness), size, and histology. FFS was decreased for patients not receiving initial radiotherapy but this did not translate into a decreased OS. The 21 patients with localized nonembryonal BP RMS had a FFS and OS of 47%. The 36 patients with metastatic disease were more likely to be older and had large tumors that were invasive with alveolar histology and regional lymph node involvement. The 5-year FFS and OS were 41 and 44%, respectively. In conclusion, the majority of BP RMS patients had localized ERMS with a resultant good prognosis using current treatment algorithms. There were differences in FFS between treatment protocols but this did not result in an altered OS.	bladder
Differential induction of reactive oxygen species through Erk1/2 and Nox-1 by FK228 for selective apoptosis of oncogenic H-Ras-expressing human urinary bladder cancer J82 cells.	PURPOSE: This study sought to reveal mechanisms for differential regulation of reactive oxygen species (ROS) in histone deacetylase inhibitor FK228-induced selective apoptosis of oncogenic H-Ras-expressing human cancer cells. METHODS: Human urinary bladder cancer J82 and oncogenic H-Ras-expressing J82 cells were used to reveal FK228-induced differential Erk1/2 activation, Nox-1 elevation, ROS production, glutathione (GSH) depletion, caspase activation, and apoptosis. Specific inhibitors were used to suppress Nox-1 activity and ROS production. Mek1/2 inhibitor was used to suppress Erk1/2 activation. Validated-specific siRNAs were used to knock down Nox-1. ROS levels, GSH levels, and caspase-3/7 activities were measured by GSH assay, flow cytometry and luminescence assays, respectively. Western blot analysis determined levels of Erk1/2 and Nox-1. RESULTS: Erk1/2, Nox-1, ROS, caspase-3/7, and cell death were differentially induced, whereas GSH was differentially depleted by FK228 in oncogenic H-Ras-expressing J82 versus parental cells. Blockage of the ERK pathway resulted in suppressing oncogenic H-Ras- and FK228-induced Nox-1 elevation, ROS production, caspase activation, and cell death. Knockdown of Nox-1 by specific siRNAs reduced FK228-induced ROS production, caspase activation, and cell death. CONCLUSION: Oncogenic H-Ras expression and FK228 treatment synergistically induced the ERK pathway, resulting in differentially increased Nox-1 elevation, ROS production, and GSH depletion, leading to differential caspase activation and cell death in oncogenic H-Ras-expressing J82 versus parental cells.	bladder
Secondary malignancies from prostate cancer radiation treatment: a risk analysis of the influence of target margins and fractionation patterns.	PURPOSE: This study explores the implications for cancer induction of treatment details such as fractionation, planning target volume (PTV) definition, and interpatient variations, which are relevant for the radiation treatment of prostate carcinomas. METHODS AND MATERIALS: Treatment planning data from 100 patients have been analyzed with a risk model based on the United Nations Scientific Committee on the Effects of Atomic Radiation competition model. The risk model can account for dose heterogeneity and fractionation effects characteristic for modern radiotherapy. Biologically relevant parameters from clinical and experimental data have been used with the model. RESULTS: The results suggested that changes in prescribed dose could lead to a modification of the risks for individual organs surrounding the clinical target volume (CTV) but that the total risk appears to be less affected by changes in the target dose. Larger differences are observed for modifications of the margins between the CTV and the PTV because these have direct impact onto the dose level and dose heterogeneity in the healthy tissues surrounding the CTV. Interpatient anatomic variations also have to be taken into consideration for studies of the risk for cancer induction from radiotherapy. CONCLUSIONS: The results have shown the complex interplay between the risk for secondary malignancies, the details of the treatment delivery, and the patient heterogeneity that may influence comparisons between the long-term effects of various treatment techniques. Nevertheless, absolute risk levels seem very small and comparable to mortality risks from surgical interventions, thus supporting the robustness of radiation therapy as a successful treatment modality for prostate carcinomas.	bladder
Age and body mass index are independent risk factors for the development of postoperative paralytic ileus after radical cystectomy.	OBJECTIVES: To identify the risk factors that would aid in the identification of patients at the greatest risk of developing postoperative paralytic ileus (POI). POI is a common complication after radical cystectomy and can result in a prolonged hospital stay and delayed recovery. METHODS: A retrospective cohort study design was used to analyze data from consecutive patients presenting to our institution for radical cystectomy with pelvic nodal dissection. POI was declared if patients were without evidence of bowel function beyond the anticipated discharge goal of 6 days. The association between several clinical features and the occurrence of POI was examined. RESULTS: Of 283 patients, 43 (15.2%) developed POI. Of the 43 patients, 38 (88.4%) were given total parenteral nutrition for nutritional supplementation. No difference in the incidence of POI was observed between the sexes, previous abdominal operations, estimated blood loss, transfusion requirement, operative time, neoadjuvant chemotherapy, or previous radiotherapy. POI was observed in 11.3% of normal and overweight patients (body mass index [BMI] <30.0 kg/m(2)) compared with 25.6% of obese patients (BMI ≥30.0 kg/m(2); P = .005). On multivariate analysis adjusted for the influence of competing variables, increasing age (hazard ratio 1.09, 95% confidence interval 1.02-1.16, P = .008) and BMI (hazard ratio 1.09, 95% confidence interval 1.03-1.17, P = .007) were significantly associated with the presence of POI. CONCLUSIONS: Our results showed that increasing age and BMI were significantly associated with the presence of POI in patients undergoing radical cystectomy for bladder cancer.	bladder
Lung carcinosarcoma.	Lung carcinosarcoma is a neoplasm of high grade composed of epithelial and mesenchymal cells. It is exceptional; and usually affects men who are smokers, between the fifth and eighth decades of life. Medical treatment, chemotherapy and radiotherapy are not active in this kind of tumour, so surgery is the treatment of choice. Prognosis is poor with survival rates at 6 months around 27%. We describe the diagnostic process and the clinical outcome of a patient with lung carcinosarcoma with several paraneoplastic syndromes.	bladder
Optical coherence tomography for bladder cancer -- ready as a surrogate for optical biopsy? Results of a prospective mono-centre study.	INTRODUCTION: New modalities like Optical Coherence Tomography (OCT) allow non-invasive examination of the internal structure of biological tissue in vivo. The potential benefits and limitations of this new technology for the detection and evaluation of bladder cancer were examined in this study. MATERIALS AND METHODS: Between January 2007 and January 2008, 52 patients who underwent transurethral bladder biopsy or TUR-BT for surveillance or due to initial suspicion of urothelial carcinoma of the bladder were enrolled in this study. In total, 166 lesions were suspicious for malignancy according to standard white light cystoscopy. All suspicious lesions were scanned and interpreted during perioperative cystoscopy using OCT. Cold cup biopsies and/or TUR-B was performed for all these lesions. For this study we used an OCT-device (Niris, Imalux, Cleveland, US), that utilizes near-infrared light guided through a flexible fibre-based applicator, which is placed into the bladder via the working channel of the cystoscope. The technology provides high spatial resolution on the order of about 10-20 microm, and a visualization of tissue to a depth of about 2 mm across a lateral span of about 2 mm in width. The device used received market clearance from the FDA and CE approval in Germany. The diagnostic and surgical procedure was videotaped and analyzed afterwards for definitive matching of scanned and biopsied lesion. The primary aim of this study was to determine the level of correlation between OCT interpretation and final histological result. RESULTS: Of 166 scanned OCT images, 102 lesions (61.4%) matched to the same site where the biopsy/TUR-BT was taken according to videoanalysis. Only these video-verified lesions were used for further analysis. Of all analyzed lesions 88 were benign (inflammation, edema, hyperplasia etc.) and 14 were malignant (CIS, Ta, T1, T2) as shown by final histo?pathology. - All 14 malignant lesions were detected correctly by OCT. Furthermore all invasive tumors were staged correctly by OCT regarding tumor growth beyond the lamina propria. There were no false negative lesions detected by OCT. Sensitivity of OCT for detecting the presence of a malignant lesion was 100% and sensitivity for detection of tumor growth beyond the lamina propria was 100% as well. Specificity of OCT for presence of malignancy was 65%, due to the fact that a number of lesions were interpreted as false positive by OCT. CONCLUSION: As a minimally invasive technique, OCT proved to have extremely high sensitivity for detection of malignant lesions as well as estimation of whether a tumor has invaded beyond the lamina propria. However, specificity of OCT within the bladder was impaired (65%), possibly due to a learning curve and/or the relatively low spatial resolution and visualization depth of the OCT technology. Further studies and technical development are needed to establish an adequate surrogate for optical biopsy.	bladder
Discrepancy between clinical staging through bimanual palpation and pathological staging after cystectomy.	OBJECTIVES: In muscle invasive bladder cancer (MIBC), careful clinical staging is essential for patient counseling and decision-making. Bimanual palpation (BP) is an integral part and guideline advice of clinical staging. Until now, however, the value of BP has never been studied. With this study, we aim to determine the accuracy of clinical staging through BP. METHODS: Detailed clinical data were collected from a population-based series of 1,409 patients with MIBC, diagnosed between 1989 and 2005, in the region of the Comprehensive Cancer Centre East in The Netherlands. Selected were all patients who underwent BP (n = 738). Preoperative tumor-stage (cT-stage) determined through BP was compared with post-cystectomy pT-stage. Contingency tables were made to determine the correlation between cT-stage and pT-stage. RESULTS: In 18 of 142 patients in whom BP showed an organ-confined tumor, the tumor was unresectable (pT4) at the time of surgery. Four out of 9 patients who had a suspected T4 tumor on BP but who underwent cystectomy anyway appeared to have operable tumors at cystectomy. In 87 patients (57.6%), accurate staging through BP was observed. In 17 patients (11.3%), clinical overstaging was found, and in 47 patients, (31.1%) clinical understaging. CONCLUSIONS: Frequently, pT-stage after cystectomy does not correlate with preoperative cT-stage based on BP. Discrepancy was observed in 42% of the patients: in 11%, clinical overstaging and in 31%, clinical understaging. Based on these data, some caution is suggested when interpreting the outcome of BP. Prospective data is needed for a more formal evaluation of the staging accuracy of BP.	bladder
Arsenic exposure in utero and nonepidermal proliferative response in adulthood in Tg.AC mice.	To expand our knowledge on the transplacental carcinogenic potential of inorganic arsenic, pregnant Tg.AC mice received drinking water with 0, 42.5, or 85 ppm arsenite from gestation day 8 to 18. After birth, groups (n = 25) of offspring received topical 12-O-tetradecanoyl phorbol-13-acetate (TPA) (2 microg twice a week) for 36 weeks and were killed; nonskin tumors were assessed. Arsenic increased adrenal cortical adenomas (ACAs; 25%-29%) compared with control (0%) independent of TPA in all male groups. Arsenic increased urinary bladder (UB) hyperplasia in males, but only with TPA. Arsenic induced ACAs in all female groups (control 0%; arsenic 17%-26%). Arsenic-treated females had UB hyperplasia in most groups (control 0%; arsenic 26%-32%), with 2 UB papillomas. All arsenic-treated females had uterine hyperplasia (26%-40%; control 4%) independent of TPA, and 3 had uterine tumors. Thus, arsenic in utero rapidly induces ACAs and uterine and UB preneoplasias in Tg.AC mice, showing transplacental carcinogenic potential in yet another strain of mice.	bladder
Tobacco-related tumours of the lung, bladder and larynx: changes in Spain.	The association between tobacco use and lung cancer and other tumours has been confirmed by a large number of studies. In Spain, the prevalence of smoking has been declining since 1978. This study describes lung, bladder and laryngeal cancer mortality and incidence rates and their trends in Spain. Mortality data were furnished by the National Statistics Institute (2001-07) and incidence data by population-based cancer registries (1975-2004). Changes in rates were calculated using Poisson regression models, which enable trend changes to be estimated. In the case of lung cancer, mortality rates decreased among men [annual percentage change (APC) -1.3%] though not among women (APC 3.5%), whereas incidence rates increased in both sexes, overall and adjusted for registry, by 0.75% among men and 3.2% among women. Bladder cancer mortality rates decreased among men (APC -1.2%) and women (APC -0.8%), yet incidence rates increased across the sexes. While laryngeal cancer mortality rates decreased among men (APC -5.5%) and women (APC -0.03%) alike, incidence rates decreased (-1.28%) among men but not among women (3.95%). A decrease in male versus female mortality due to tobacco-related tumours is evident in Spain. Incidence rates are beginning to reflect the progressive cessation of smoking that has been observed among men rather than women.	bladder